Prostaglandins have been proposed as mediators of inflammation but their functions in human rheumatic diseases are unclear. Other investigators have previously proposed that the effects of nonsteroidal anti-inflammatory drugs are accounted for by their inhibition of prostaglandin biosynthesis. This project investigates the synthesis of prostaglandins by rheumatoid and normal synovial tissues in vitro. Explants of synovia were shown to produce PGE2 and PGF2 alpha in preliminary experiments. Prostaglandins are measured by a combination of radioimmunoassay and thin layer chromatographic techniques. Inhibitory effects of various anti-inflammatory drugs will be studied in this system. A new finding of potent inhibition of prostaglandin synthesis by anti-inflammatory corticosteroids will be further investigated in detail. Prostaglandin synthesis will also be studied by microsomal preparations from synovial tissues in order to characterize the biochemical properties of the prostaglandin synthetase in synovia, and to clarify the mechanisms of inhibition of prostaglandin synthesis by corticosteroids and other anti-inflammatory drugs. Comparison of results obtained from rheumatoid, osteoarthritic and normal synovia is planned. Fibroblast cell lines derived from explants of rheumatoid, osteoarthritis and normal synovia and skin will be examined for prostaglandin production, and compared with cyclic AMP and cyclic GMP levels in these cells. Investigation of the observed stimulation of prostaglandin synthesis by microtubule active agents, colchicine and vinblastin may help clarify mechanisms of regulation of prostaglandin biosynthesis.